Table 1.

Proposed neuropathogenic mechanisms in SARS-CoV-2 infection

Acute neurological syndromes	Proposed mechanisms	References	Proposed therapies
Anosmia/ageusia	Direct infection of olfactory bulb Inflammation of olfactory tract	Meinhardt et al.,14 Lu et al.15	None
Stroke	Hypercoagulability/endothelial damage	Hernández-Fernández et al.,16 Goshua et al.,17 Yaghi et al.18	Prophylactic anticoagulation is currently under investigation; no clear guidelines to date   Successful treatment with thrombolysis and mechanical thrombectomy reported
Encephalitis	Viral neuro-invasion	Nampoothiri et al.,19 Meinhardt et al.14	Favourable responses to systemic corticosteroids, tocilizumab, and PLEX are observed in a subset of cases
	Disrupted blood–brain barrier	Alexopoulos et al.20
	Autoimmunity	Cao et al.,21 Guilmot et al.,22 Pilotto et al.23,24
Encephalopathy	Metabolic dysfunction   Hypoxia/ischaemia   Cerebral microthrombi   Cytokine storm (systemic)	Bryce et al.,25 Antony and Haneef,26 Lee et al.,27 Lin et al.28	Generally supportive, reported success with tocilizumab in case reports
Peripheral neuropathy	Critical illness neuropathy	Cabañes-Martínez et al.29	Supportive
	Molecular mimicry (GBS and variants)	Dalakas,30 Temme et al.31	Standard therapy: IVIg, PLEX
Myositis	Bioenergetic dysfunction   Immune-mediated myositis	Beydon et al.,32 Dalakas,30 Zhang et al.33	Favourable responses to steroids, IVIg and tocilizumab reported
Chronic neurological sequelae
Fatigue	Chronic neuroinflammation   Neuroendocrine dysfunction   Persistent respiratory and cardiac damage	Pandharipande et al.,34 Raman et al.,35 Mongioì et al.36	None
Cognitive impairment	Chronic neuroinflammation   Frontoparietal hypometabolism	Blazhenets et al.,37 Guedj et al.38	None, demonstrated to improve over months
Depression/altered mood	Stress (isolation, post-traumatic stress)	Rogers et al.39	No specific therapies proposed or tested for post-COVID-19 patients

PLEX = plasma exchange.